Optically active alkylammonium 1-(3-aminophenyl)-ethanesulphonate derivatives, their preparation and their use

ABSTRACT

This invention relates to levogyral isomers of alkylammonium (amino-3 phenyl)-1 ethanesulphonate derivatives of formula (I) in which R+ denotes a tetraalkylammonium or trialkylphenylalkylammonium residue. The invention also concerns the preparation and use of said derivatives.

DESCRIPTION OF THE INVENTION

The present invention relates to the laevorotatory isomers ofalkylammonium 1-(3-aminophenyl)ethanesulphonates of formula: ##STR1## inwhich R⁺ represents a tetraalkylammonium or trialkylphenylalkylammoniumresidue, to their preparation and their use as intermediates in thepreparation of compounds which are useful as cholecystokinin (CCK) andgastrin antagonists.

In the preceding definitions, and in those which follow, the alkylradicals contain 1 to 4 carbon atoms in a straight or branched chain.They preferably represent the n-butyl radical.

The compounds of formula (I) (laevorotatory isomers) can be prepared inaccordance with the following process:

a) action of an alkali metal sulphite on(RS)-1-(1-bromoethyl)-3-nitrobenzene and, if necessary, conversion tothe potassium salt to give potassium(RS)-1-(3-nitrophenyl)ethanesulphonate,

b) conversion of the potassium salt obtained in a) into a mixture of theA and B forms of benzylquininium 1-(3-nitrophenyl)ethanesulphonate,separation of the A form and recovery of a mixture enriched in the Bform,

c) conversion of the benzylquininium salt, enriched in the B form,obtained in b) into potassium 1-(3-nitrophenyl)ethanesulphonate,thereafter into phenylglycinol 1-(3-nitrophenyl)ethanesulphonate, Bform, and finally into the tetraalkylammonium ortrialkylphenylalkylammonium 1-(3-nitrophenyl)-ethanesulphonate(laevorotatory isomer)

d) reduction of the product obtained in c) to give the compound offormula (I) (laevorotatory isomer).

It is particularly advantageous to carry out stage a) in aqueoussolution at a temperature of between 50° C. and 100° C. and preferablyat 80° C.

The alkali metal sulphite is preferably sodium sulphite or potassiumsulphite.

To recover the product, it is preferable to convert it to thetetraalkylammonium or trialkylphenylammonium salt, isolate this and thenconvert it to the potassium salt.

Stage b) is preferably carried out by means of an N-benzylquininiumhalide, and preferably the chloride, in the presence of potassiumdihydrogenphosphate in an aqueous medium and at a temperature of between10° C. and 30° C. in particular at a temperature of about 20° C.

The potassium salt of stage c) is obtained by treatment with potassiumnonafluorobutanesulphonate, in an inert solvent such as acetone, at atemperature of between 10° C. and 30° C., and preferably at 20° C.

The phenylglycinol salt of stage c) is obtained by treatment with(R)-(-)-phenylglycinol in the presence of an acid such as hydrochloricacid, in an aqueous medium, at a temperature of between 10° C. and 30°C. and preferably at 20° C.

The phenylglycinol salt is thereafter converted to the compound offormula (I) by means of a tetraalkylammonium ortrialkylphenylalkylammonium salt, preferably the hydrogensulphates, inan aqueous medium, at a temperature of between 10° C. and 30° C. andpreferably at 20° C.

The reduction of stage d) is generally carried out under hydrogenpressure, in the presence of a hydrogenation catalyst such as palladium,in an inert solvent such as an alcohol (for example ethanol), at atemperature of about 25° C. Preferably, a hydrogen pressure of 100 kPais used.

The compounds of formula (I) (laevorotatory isomers) are particularlyvaluable as intermediates for the preparation of the enantiomers of thecompounds of formula: ##STR2## and their salts.

In formula (II), A represents:

A) a --CH₂ --CO--NR₁ R₂ residue, in which R₁ represents one of thefollowing radicals: (a) phenyl optionally substituted by one or moresubstituents chosen from among halogen atoms and alkyl, alkoxy, hydroxylpolyfluoroalkyl, nitro, alkylthio, alkoxycarbonyl, carboxyl, acylamino,methylenedioxy, polyfluoroalkoxy, trifluoromethylthio, phenoxy, phenyl,benzyl, phenylamino and CONR₃ R₄ radicals, which may be identical ordifferent, represent a hydrogen atom or an alkyl, phenyl (optionallysubstituted by one or more substituents chosen from among halogen atomsand alkyl, alkoxy and alkylthio radicals), indanyl, cycloalkylalkyl,cycloalkyl or phenylalkyl radical or else R₃ and R₄ together with thenitrogen atom to which they are attached form a saturated or unsaturatedmonocyclic or polycyclic heterocyclic ring containing 4 to 9 carbonatoms and one several heteroatoms (O, N or S) and optionally substitutedby one or several alkyl, alkoxy, alkoxycarbonyl, dialkylcarbamoyl orphenyl radicals or, in combination with a carbon atom of theheterocyclic ring, by a spiromonocyclic ring having 4 or 5 members andoptionally containing one or more heteroatoms (O, S or N); b) pyridyl,c) isoquinolyl, d) quinolyl, e) quinoxalinyl (these heterocyclic ringsbeing optionally substituted by one or more substituents chosen fromamong alkyl and phenyl radicals and halogen atoms), f) alkyl, g)phenylalkyl, h) naphthyl, i) 5,6,7,8-tetrahydronaphthyl, j)1,2,3,4-tetrahydronaphthyl, k) alkoxycarbonylalkyl or 1) cycloalkyl. R₂represents a --CH(R₅)--CO--R₆ chain in which R₅ represents a hydrogenatom or an alkyl or alkoxycarbonyl radical or a phenyl radical(optionally substituted by one or more substituents chosen from amonghalogen atoms and alkyl, alkoxy, alkylthio, nitro and amino radicals),and R₆ represents an alkoxy, cycloalkoxy (optionally substituted by atleast one alkyl radical), cycloalkylalkoxy, phenylalkoxy,polyfluoroalkoxy cinnamyloxy radical and --NR₃ R₄.

B) a residue of formula: ##STR3## in which: either R represents amethylene, ethylene, SO, SO₂ or CHOH radical or a sulphur atom, R₇represents a pyridyl radical optionally substituted by one or more alkylradicals, a furyl radical optionally substituted by one or more alkylradicals, a thienyl radical optionally substituted by one or more alkylradicals, a quinolyl radical optionally substituted by one or more alkylradicals, a naphthyl radical optionally substituted by one or more alkylradicals, an indolyl radical optionally substituted by one or more alkylradicals or phenyl optionally substituted by one or more substituentschosen from among halogen atoms and alkyl, alkoxy, hydroxyl, nitro,amino, monoalkylamino, dialkylamino, alkoxycarbonyl, --CO--NR₁₁ R₁₂,--NH--CO--CH₃, trifluoromethyl or trifluoromethoxy radicals and R₈represents a hydrogen atom,

or R represents a methylene radical, R₇ represents a hydrogen atom andR₈ represents a phenyl radical,

or R represents a CHR₁₃ radical, and R₇ and R₈ each represent a hydrogenatom,

R₉ represents an alkoxycarbonyl, cycloalkoxycarbonyl,cycloalkylalkoxycarbonyl or --CONR₁₄ R₁₅ radical or a phenyl radicaloptionally substituted by one or more substituents chosen from amongalkyl, alkoxy or hydroxyl radicals,

R₁₀ represents a hydrogen atom or an alkyl radical,

R₁₃ represents a phenyl radical,

R₁₁ represents a hydrogen atom or one of the following radicals: alkyl,phenylalkyl or phenyl optionally substituted by one or more substituentschosen from among halogen atoms and alkyl, alkoxy and alkylthioradicals,

R₁₂ represents one of the following radicals: alkyl, phenylalkyl orphenyl optionally substituted by one or more substituents chosen fromamong halogen atoms and alkyl, alkoxy and alkylthio radicals, or elseR₁₁ and R₁₂, together with the nitrogen atom to which they are attached,form a monocyclic or polycyclic, saturated or unsaturated, heterocyclicring which contains 4 to 9 carbon atoms and one or more heteroatoms (Oor N) and is optionally substituted by one or more alkyl radicals,

R₁₄ represents a hydrogen atom or one of the following radicals: alkyl,cycloalkylalkyl, cycloalkyl, phenylalkyl or phenyl optionallysubstituted by one or more substituents chosen from among halogen atomsand alkyl, alkoxy and alkylthio radicals,

R₁₅ represents one of the following radicals: alkyl, cycloalkylalkyl,cycloalkyl, phenylalkyl or phenyl optionally substituted by one or moresubstituents chosen from among halogen atoms and alkyl, alkoxy andalkylthio radicals, or else R₁₄ and R₁₅ together with the nitrogen atomto which they are attached form a monocyclic or polycyclic, saturated orunsaturated, heterocyclic ring which contains 4 to 9 carbon atoms andone or more heteroatoms (O, N or S) and is optionally substituted by oneor more alkyl radicals,

C) a residue of formula: ##STR4## in which: R₁₆ represents a hydrogen orhalogen atom or an alkyl, alkylthio, nitro, hydroxyl or cyano radical,

R₁₇ represents an alkyl radical or a --CH(R₅)--CO--R₆ residue,

R₁₈ represents a pyridyl radical or phenyl radical optionallysubstituted by one or more substituents chosen from among halogen atomsand alkyl, alkoxy, hydroxyl, carboxyl, and nitro radicals.

In the definitions of the compounds of formula (II), the alkyl andalkoxy radicals and the alkyl and alkoxy moieties preferably contain 1to 4 carbon atoms in a straight or branched chain, the cycloalkylradicals and moieties 3 to 6 carbon atoms and the acyl radicals 2 to 4carbon atoms.

These compounds are described in Patent Applications WO 91/12264, WO91/13907, WO 91/13874, FR 9108675 and FR 9112481 as being antagonistsfor cholecystokinin and gastrin.

The compounds of formula (II) can be prepared from the compounds offormula (I) by proceeding as follows:

a compound of formula (I) is caused to act on a derivative of formula:##STR5## in which a has the same meanings as in formula (II).

This reaction is generally carried out in an inert solvent such astetrahydrofuran, dimethylformamide, a chlorinated solvent or an aromaticsolvent (for example benzene or toluene), at a temperature of between20° C. and the boiling point of the solvent.

The derivatives of formula (III) can be prepared in accordance with theprocesses described in Patent Applications WO 91/12264, WO 91/13907, WO91/13874, FR 9108675 and FR 9112481.

EXAMPLES

EXAMPLE 1

a) potassium (RS)-1-(3-nitrophenyl)ethanesulphonate:

25.3 g of (RS)-1-(1-bromoethyl)-3-nitrobenzene are added to a solutionof 20.8 g of sodium sulphite in 260 cm³ of water. The reaction mixtureis stirred at 80° C. for 5 hours, cooled to about 25° C. and run into2.5 liters of an aqueous 0.5M potassium dihydrogenphosphate solution, towhich 40 g of tetra-n-butylammonium hydrogen sulphate are added. Themixture is extracted with 3 times 500 cm³ of methylene chloride. Thecombined organic phases are washed with twice 500 cm³ of water, driedover magnesium sulphate and concentrated to dryness under reducedpressure (2.7 kPa) at 40° C. The oil obtained is dissolved in 65 cm³ ofacetone and 34 g of potassium nonafluorobutanesulphonate dissolved in 75cm³ of acetone are added. The insoluble product is filtered off, washedwith 3 times 50 cm³ of diisopropyl ether and dried in air. 22.4 g ofpotassium (RS)-1-(3-nitrophenyl)ethanesulphonate, melting at atemperature above 260° C., are thus obtained and are used as such in thesubsequent syntheses.

    ______________________________________                                        NMR spectrum: (200 MHz; DMSO d)                                               δ (ppm):                                                                ______________________________________                                        1.50       [d, J=7 Hz, 3H: --CH(CH.sub.3)--]                                  3.93       [q, J=7 Hz, 1H: --CH(CH.sub.3)--]                                  7.59       [t, J=8 Hz, 1H: --C.sub.6 H.sub.4 (--H5)]                          7.83       [d, J=8 Bz, 1H: --C.sub.6 H.sub.4 (--H6)]                          8.10       [broad d, J=8 Hz, 1H: --C.sub.6 H.sub.4 (--H4)]                    8.26       [broad s, 1H: --C.sub.6 H.sub.4 (--H2)]                            ______________________________________                                    

(RS)-1-(1-Bromoethyl)-3-nitrobenzene can be prepared in accordance withthe method described by E. Felder et al., J. Med. Chem., 13, 559 (1970).

b) mixture of the A and B forms of N-benzylquininium1-(3-nitrophenyl)ethanesulphonate:

87 g of potassium dihydrogenphosphate and 32.4 g of N-benzylquininiumchloride are added to a solution of 17.2 g of potassium(RS)-1-(3-nitrophenyl)ethanesulphonate in 400 cm³ of water. The mixtureis extracted with twice 300 cm³ of methylene chloride. The combinedorganic phases are washed with twice 200 cm³ of water, dried overmagnesium sulphate and concentrated to dryness under reduced pressure(2.7 kPa)) at 40° C. The froth obtained is dissolved in 120 cm³ of2-propanol under reflux. After cooling, the crystals are filtered offand washed with twice 15 cm³ of 2-propanol. After 2 recrystallizations,from 350 and then from 500 cm³ of 2-propanol, 15.6 g of the A form ofN-benzylquininium 1-(3-nitrophenyl)ethanesulphonate are obtained,melting at about 110° C. [α]_(D) ²⁰ =-151.3°±1.5 (C=1.009%; methanol).The propanol solutions are combined and concentrated to dryness underreduced pressure (2.7 kPa) at 45° C. 25.0 g of a mixture of the A and Bforms (about 15/85 in moles) of N-benzylquininium1-(3-nitrophenyl)ethanesulphonate are thus obtained.

c) laevorotatory isomer of tetra-n-butylammonium1-(3-nitrophenyl)ethanesulphonate:

5.2 g of potassium nonafluorobutanesulphonate dissolved in 12 cm³ ofacetone are added to a solution of 10.5 g of a mixture of the A and Bforms (about 15/85 in moles) of N-benzylquininium1-(3-nitrophenyl)ethanesulphonate in 16 cm³ of acetone. The insolubleproduct is filtered off and then dissolved in 9 cm³ of water. 8.4 cm³ ofan aqueous 1N hydrochloric acid solution and 1.15 g of(R)-(-)-phenylglycinol are added. The solution obtained is concentratedto dryness under reduced pressure (2.7 kPa) at 50° C. The residueobtained is extracted with 3 times 15 cm³ of acetonitrile under reflux.The organic phases are combined and concentrated to about 7 cm³ ; aftercooling, the crystals are filtered off and dissolved in 7.5 cm³ of anaqueous 1N sodium hydroxide solution. The solution obtained is washedwith 8 times 25 cm³ of diethyl ether, after which 60 cm³ of an aqueous0.5M solution of potassium dihydrogenphosphate and 2.3 g oftetra-n-butylammonium hydrogensulphate are added. The mixture isextracted with 3 times 30 cm³ of methylene chloride. The combinedorganic phases are dried over magnesium sulphate and concentrated todryness under reduced pressure (2.7 kPa) at 40° C. 2.8 g of thelaevorotatory isomer of tetra-n-butylammonium1-(3-nitrophenyl)ethanesulphonate are thus obtained in the form of anoil which is used as such in the subsequent syntheses.

d) laevorotatory isomer of tetra-n-butylammonium1-(3-aminophenyl)ethanesulphonate:

0.2 g of 5% strength palladium on charcoal is added to a solution of 2.8g of the laevorotatory isomer of tetra-n-butylammonium1-(3-nitrophenyl)ethanesulphonate in 50 cm³ of ethanol. The suspensionis stirred for 2 hours at a temperature of about 25° C. under a hydrogenatmosphere (100 kPa). The catalyst is filtered off and the filtrate isconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 2.8 gof the laevorotatory isomer of tetra-n-butylammonium1-(3-aminophenyl)ethanesulphonate are thus obtained in the form of anoil, used as such in the subsequent syntheses.

    ______________________________________                                        NMR spectrum: (200 MHz; CDCl.sub.3, B form)                                   δ (ppm):                                                                ______________________________________                                        0.98        (t, J=7 Hz, 12H: --CH.sub.3 of the butyl)                         from 1.25 to 1.65                                                                         (mt, 16H: --CH.sub.2 --CH.sub.2 --CH.sub.3 of the butyl)          1.65        (d, J=7 Hz, 3H: --CH(CH.sub.3)                                    2.95        (mf , 2H: --NH.sub.2)                                             3.15        (mt, 8H: >N--(CH.sub.2 --) of the butyl)                          3.91        (q, J=7 Hz, 1H: --CH(CH.sub.3)--)                                 6.50        (d, broad, J=8 Hz, 1H: --C.sub.6 H.sub.4 (H4)                     6.85        (d, J=8 Hz, 1H: --C.sub.6 H.sub.4 (H6))                           6.86        (s broad, 1H: --C.sub.6 H.sub.4 (H2))                             7.00        (t, J=8 Hz, 1H: --C.sub.6 H.sub.4 (H5))                           ______________________________________                                    

APPLICATION EXAMPLE

2.7 g of the laevorotatory isomer of tetra-n-butylammonium1-(3-aminophenyl)ethanesulphonate are added to a solution of 2.1 g of2-{2-[(imidazolyl-1)carboxamido]-N-(3-methoxyphenyl)acetamido}-N-methyl-N-phenyl-acetamidein 130 cm³ of toluene. The reaction mixture is stirred under reflux for5 hours and then concentrated to dryness under reduced pressure (2.7kPa) at 45° C. The residue is dissolved in 100 cm³ of methylene chlorideand the solution obtained is washed with 50 cm³ of an aqueous 2Nhydrochloric acid solution and then with twice 50 cm³ of water. Theorganic phase is dried over magnesium sulphate and concentrated todryness under reduced pressure (2.7 kPa ) at 40° C. The crude productobtained is stirred for 30 minutes in 50 cm³ of diisopropyl ether. Theinsoluble product is filtered off and then dissolved in 6 cm³ ofacetone. 1.2 g of potassium nonafluorobutanesulphonate dissolved in 3cm³ of acetone are added, followed by 5 cm³ of diisopropyl ether. Theinsoluble gum is separated off and then stirred for 1 hour in 12 cm³ ofa mixture of acetone and diisopropyl ether (50/50 by volume). Theinsoluble product is filtered off, washed with twice 5 cm³ of a mixtureof acetone and diisopropyl ether (50/50 by volume) and then 4 times 5cm³ of diisopropyl ether and is dried in air. 1.55 g of potassium(-)-1-{3-{3-[N-(3-methoxyphenyl)-N-(N-methyl-N-phenylcarbamoylmethyl)carbamoylmethyl]ureido}phenyl}ethanesulphonate,melting at about 180° C., are thus obtained. [α]_(D) ²⁰ =-5.0°±0.5(C=0.888%; Methanol).

    ______________________________________                                        NMR spectrum: (300 MHz; DMSO d6: (-) form)                                    δ (ppm):                                                                ______________________________________                                        1.43        [d, J=7 Hz, 3H: --CH(CH.sub.3)--]                                 3.18        [broad s, 3H: --N(CH.sub.3)--]                                    3.60        [mt, 1H: --CH(CH.sub.3)--]                                        3.65        [broad d, J=5 Hz, 2H: --CO(CH.sub.2)NH--]                         3.79        (s, 3H, --OCH.sub.3)                                              4.09        [mf, 2H: --CO(CH.sub.2)N<]                                        6.28        [broad t, J=5 Hz, 1H: --NH--]                                     6.86        [d, J=7.5 Hz, 1H: --C.sub.6 H.sub.4 (--H4) of the                             N-(3-Methoxyphenyl)]                                              from 6.95 to 7.15                                                                         (mt, 4H: aromatics)                                               7.17        (broad s, 1H: --C.sub.6 H.sub.4 (--H2) of the N--                             (3-methoxyphenyl)]                                                from 7.30 to 7.50                                                                         (mt, 11H: aromatics)                                              8.80        (broad s, 1H: --CO--NH--Ar).                                      ______________________________________                                    

2-{2-[(1-Imidazolyl)carboxamido]-N-(3-methoxyphenyl)acetamido}-N-methyl-N-phenylacetamidecan be prepared in the following manner: a solution of 3.1 g of2-[2-amino-N-(3-methoxyphenyl)acetamido]-N-methyl-N-phenylacetamide in30 cm³ of anhydrous tetrahydrofuran is added to a solution of 3.0 g ofN,N'-dimidazolecarbonyl in 30 cm³ of anhydrous tetrahydrofuran. Thesolution is stirred for 16 hours at a temperature of about 25° C. andthen concentrated to dryness under reduced pressure (2.7 kPa) at 40° C.The residue is dissolved in 50 cm³ of ethyl acetate and the solutionobtained is washed with 4 times 30 cm³ of water. The organic phase isdried over magnesium sulphate and then concentrated to dryness underreduced pressure (2.7 kPa) at 40° C. After recrystallization from ethylacetate, 3.5 g of2-{2-[(1-imidazolyl)carboxamido]-N-(3-methoxyphenyl)acetamido}-N-methyl-N-phenylacetamide,melting at 146° C., are obtained.

2-[2-Amino-N-(3-methoxyphenyl)acetamido]-N-methyl-N-phenylacetamide canbe prepared in the following manner: 1.3 g of hydrazine hydrate areadded to a solution of 5.5 g of2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]-N-methyl-N-phenylacetamidein 60 cm³ of methanol. The reaction mixture is stirred under reflux for30 minutes and, after cooling, 100 cm³ of water are added. The mixtureis concentrated to about 100 cm³ and then brought to pH 9 with anaqueous 2N sodium hydroxide solution and extracted with twice 50 cm³ ofethyl acetate. The combined organic phases are washed with twice 50 cm³of water, dried over magnesium sulphate and then concentrated to drynessunder reduced pressure (2.7 kPa) at 40° C. 3.0 g of2-[2-amino-N-(3methoxyphenyl)acetamido]-N-methyl-N-phenylacetamide arethus obtained in the form of an oil, which is used as such in thesubsequent syntheses.

2-[N-(3-Methoxyphenyl)-2-phthalimidoacetamido]-N-methyl-N-phenylacetamidecan be prepared in the following manner: 10 cm³ of dimethylformamide areadded to a suspension of 80.6 g of2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]acetic acid in 900 cm³ of1,2-dichloroethane, after which 30.2 g of oxalyl dichloride are addedover 1 hour. The mixture is stirred for 2 hours at a temperature ofabout 25° C., after which 58.6 g of N-methylaniline are added over 45°minutes. The reaction mixture is stirred for 2 hours at a temperature ofabout 25° C. washed with twice 500 cm³ of water and then with 300 cm³ ofa saturated aqueous sodium bicarbonate solution, is dried over magnesiumSulphate and is concentrated to dryness under reduced pressure (2.7 kPa)at 40° C. The residue is stirred for one hour in 300 cm³ of diisopropylether and the insoluble product is filtered off, washed with 3 times 60cm³ of diisopropyl ether and dried in air. 84 g of2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]-N-methyl-N-phenylacetamide,melting at 137° C., are thus obtained.

2-[N-(3-Methoxyphenyl)-2-phthalimidoacetamido]acetic acid can beprepared in the following manner: 74.0 g of trifluoroacetic acid areadded to a solution of 42.0 g of tert-butyl2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]acetate in 500 cm³ ofmethylene chloride. The solution obtained is stirred under reflux for 5hours and then concentrated to--dryness under reduced pressure (2.7 kPa)at 40° C. The residue is stirred for one hour in 100 cm³ of diisopropylether and the insoluble product is filtered off, washed with 3 times 40cm³ of diisopropyl ether and dried in air. 36 g of2-[N-(3-methoxyphenyl)-2phthalimidoacetamido]acetic acid, melting at203° C., are thus obtained.

tert-Butyl 2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]acetate can beprepared in the following manner: 14.9 g of an oily suspension (60 % byweight) of sodium hydride are added, over 30 minutes, to a solution of96 g of N-(3-methoxyphenyl)-2-phthalimidoacetamide in 1000 cm³ ofanhydrous tetrahydrofuran. The suspension is stirred for 4 hours at atemperature of about 20° C., after which 72.7 g of tert-butylbromoacetate are added over 15 minutes. The reaction mixture is stirredfor 16 hours at a temperature of about 25° C., hydrolyzed slowly with 50cm³ of water and then concentrated to dryness under reduced pressure.The residue obtained is stirred for one hour in 400 cm³ of water and theinsoluble product is filtered off, washed with 3 times 100 cm³ of waterand twice 100 cm³ of diisopropyl ether and dried in air. 82.0 g oftert-butyl 2-[N-(3-methoxyphenyl)-2-phthalimidoacetamido]acetate,melting at 148° C., are thus obtained.

N-(3-Methoxyphenyl)-2-phthalimidoacetamide can be prepared in thefollowing manner: 22.0 g of triethylamine followed by 48.0 g of2-phthalimidoacetyl chloride dissolved in 300 cm³ of methylene chlorideare added to a solution of 26.0 g of 3-methoxyaniline in 200 cm³ ofmethylene chloride, whilst keeping the temperature at about 20° C. Thereaction mixture is stirred for 4 hours at this temperature and 800 cm³of water are then added. The insoluble product is filtered off, washedwith 3 times 100 cm³ of water and dried in air. 65.0 g ofN-(3-methoxyphenyl)-2-phthalimidoacetamide, melting at 171° C., are thusobtained.

2-Phthalimidoacetyl chloride can be prepared in accordance with themethod described by W. Grassmann and E. Schulte-Uebbing, Chem. Ber., 83,244-247, (1950).

Although the invention has been described in conjunction with specificembodiments, it is evident that many alternatives and variations will beapparent to those skilled in the art in light of the foregoingdescription. Accordingly, the invention is intended to embrace all ofthe alternatives and variations that fall within the spirit and scope ofthe appended claims. The above references are hereby incorporated byreference.

I claim:
 1. The laevorotatory isomers of alkylammonium1-(3-aminophenyl)ethanesulphonates of formula: ##STR6## in which R⁺represents a tetraalkylammonium or trialkylphenylalkylammonium residue.2. Process for the preparation of the compounds of formula (I) accordingto claim 1, which comprises the following stages:a) action of an alkalimetal sulphite on (RS)-1-(1-bromoethyl)-3-nitrobenzene and conversion tothe potassium salt to give potassium(RS)-1-(3-nitrophenyl)ethanesulphonate, b) conversion of the potassiumsalt obtained in a) into a mixture of the A and B forms ofbenzylquininium 1-(3-nitrophenyl)ethanesulphonate, separation of the Aform and recovery of a mixture enriched in the B form, c) conversion ofthe benzylquininium salt, enriched in the B form, obtained in b) intopotassium 1-(3-nitrophenyl)ethanesulphonate, thereafter intophenylglycinol 1-(3-nitrophenyl)ethanesulphonate, B form, and finallyinto the tetraalkylammonium or trialkylphenylalkylammonium1-(3-nitrophenyl)-ethanesulphonate (laevorotatory isomer), d) reductionof the product obtained in c) to give the compound of formula (I),laevorotatory isomer.
 3. Process according to claim 2, wherein stage a)is carried out in aqueous solution at a temperature of between 50° C.and 100° C.
 4. Process according to claim 3, wherein the temperature is80° C.
 5. Process according to claim 3, wherein the recovery of theproduct is effected via a tetraalkylammonium ortrialkylphenylalkylammonium salt.
 6. Process according to claim 2,wherein stage b) is effected by means of an N-benzylquininium halide, inthe presence of potassium dihydrogenphosphate in an aqueous medium at atemperature of between 10° C. and 30° C.
 7. Process according to claim6, wherein N-benzylquininium chloride is used.
 8. Process according toclaim 2, wherein sodium sulphite or potassium sulphite is used. 9.Process according to claim 2, wherein the potassium salt of stage c) isobtained by the action of potassium nonafluorobutanesulphonate in aninert solvent at a temperature of between 10° C. and 30° C.
 10. Processaccording to claim 2, wherein in stage c), the phenylglycinol salt isobtained by the action of (R)-(-)-phenylglycinol in the presence of anacid, in an aqueous medium, at a temperature of between 10° C. and 30°C.
 11. Process according to claim 2, wherein in stage c), the conversionto an alkylammonium salt or trialkylphenylalkylammonium salt is effectedby means of a tetraalkylammonium or trialkylphenylalkylammonium salt, inan aqueous medium, at a temperature of 20° C.
 12. Process according toclaim 11, wherein a tetraalkylammonium hydrogensulphate ortrialkylphenylalkylammonium hydrogensulphate is used.
 13. Processaccording to claim 2, wherein the reduction is effected under hydrogenpressure, in the presence of a hydrogenation catalyst, in an inertsolvent and at a temperature of about 25° C.
 14. Process according toclaim 13, wherein a hydrogen pressure of 100 kPa is used.
 15. Processaccording to claim 2, for the preparation of the laevorotatory isomer of(tetra-n-butyl)ammonium 1-(3-aminophenyl)ethanesulphonate.
 16. A methodof using the compounds according to claim 1 for the preparation ofenantiomers of the compounds of formula II: ##STR7## in which Arepresents A) a --CH₂ --CO--NR₁ R₂ residue, in which R₁ represents oneof the following radicals (a) phenyl optionally substituted by at leastone substituent selected from among halogen atoms and alkyl, alkoxy,hydroxyl polyfluoroalkyl, nitro, alkylthio, alkoxycarbonyl, carboxyl,acylamino, methylenedioxy, polyfluoroalkoxy, trifluoromethylthio,phenoxy, phenyl, benzyl, phenylamino and CONR₃ R₄ radicals, which may beidentical or different, represent a hydrogen atom or an alkyl, phenyl(optionally substituted by at least one substituent selected from amonghalogen atoms and alkyl, alkoxy and alkylthio radicals), indanyl,cycloalkylalkyl, cycloalkyl or phenylalkyl radical or else R₃ and R₄together with the nitrogen atom to which they are attached form asaturated or unsaturated monocyclic or polycyclic heterocyclic ringcontaining 4 to 9 carbon atoms and at lease one heteroatom selected fromO, N and S and optionally substituted by one alkyl, alkoxy,alkoxycarbonyl, dialkylcarbamoyl or phenyl radical or, in combinationwith a carbon atom of the heterocyclic ring, by a spiromonocyclic ringhaving 4 or 5 members and optionally containing at least one heteroatomselected from O, S and N; b) pyridyl, c) isoquinolyl, d) quinolyl, e)quinoxalinyl (these heterocyclic rings being optionally substituted byat least one substituent selected from among alkyl and phenyl radicalsand halogen atoms), f) alkyl, g) phenylalkyl, h) naphthyl, i)5,6,7,8-tetrahydronaphthyl, j) 1,2,3,4-tetrahydronaphthyl, k)alkoxycarbonylalkyl or 1) cycloalkyl, R₂ represents a --CH(R₅)--CO--R₆chain in which R₅ represents a hydrogen atom or an alkyl oralkoxycarbonyl radical or a phenyl radical (optionally substituted by atleast one substituent selected from among halogen atoms and alkyl,alkoxy, alkylthio, nitro and amino radicals), and R₆ represents analkoxy, cycloalkoxy (optionally substituted by at least one alkylradical), cycloalkylalkoxy, phenylalkoxy, polyfluoroalkoxy cinnamyloxyradical and --NR₃ R₄,B) a residue of formula: ##STR8## in which: eitherR represents a methylene, ethylene, SO, SO₂ or CHOH radical or a sulphuratom, R₇ represents a pyridyl radical optionally substituted by at leastone alkyl radical, a furyl radical optionally substituted by at leastone alkyl radical, a thienyl radical optionally substituted by at leastone alkyl radical, a quinolyl radical optionally substituted by at leastone alkyl radical, a naphthyl radical optionally substituted by at leastone alkyl radical, an indolyl radical optionally substituted by at leastone alkyl radical or phenyl optionally substituted by at least onesubstituent selected from among halogen atoms and alkyl, alkoxy,hydroxyl, nitro, amino, monoalkylamino, dialkylamino, alkoxycarbonyl,--CO--NR₁₁ R₁₂, --NH--CO--CH₃, trifluoromethyl or trifluoromethoxyradicals and R₈ represents a hydrogen atom,or R represents a methyleneradical, R₇ represents a hydrogen atom and R₈ represents a phenylradical, or R represents a CHR₁₃ radical, and R₇ and R₈ each represent ahydrogen atom, R₉ represents an alkoxycarbonyl, cycloalkoxycarbonyl,cycloalkylalkoxycarbonyl or --CONR₁₄ R₁₅ radical or a phenyl radicaloptionally substituted by at least one substituent selected from amongalkyl, alkoxy or hydroxyl radicals, R₁₀ represents a hydrogen atom or analkyl radical, R₁₃ represents a phenyl radical, R₁₁ represents ahydrogen atom or one of the following radicals: alkyl, phenylalkyl orphenyl optionally substituted by at least one substituent selected fromamong halogen atoms and alkyl, alkoxy and alkylthio radicals, R₁₂represents one of the following radicals: alkyl, phenylalkyl or phenyloptionally substituted by at least one substituent selected from amonghalogen atoms and alkyl, alkoxy and alkylthio radicals, or else R₁₁ andR₁₂, together with the nitrogen atom to which they are attached, form amonocyclic or polycyclic, saturated or unsaturated, heterocyclic ringwhich contains 4 to 9 carbon atoms and at least one heteroatom selectedfrom O or N and is optionally substituted by at least one alkyl radical,R₁₄ represents a hydrogen atom or one of the following radicals: alkyl,cycloalkylalkyl, cycloalkyl, phenylalkyl or phenyl optionallysubstituted by at least one substituent selected from among halogenatoms and alkyl, alkoxy and alkylthio radicals, R₁₅ represents one ofthe following radicals: alkyl, cycloalkylalkyl, cycloalkyl, phenylalkylor phenyl optionally substituted by at least one substituent selectedfrom among halogen atoms and alkyl, alkoxy and alkylthio radicals, orelse R₁₄ and R₁₅ together with the nitrogen atom to which they areattached form a monocyclic or polycyclic, saturated or unsaturated,heterocyclic ring which contains 4 to 9 carbon atoms and at least oneheteroatom selected from O, N and S and is optionally substituted by atleast one alkyl radical, C ) a residue of formula: ##STR9## in which:R₁₆ represents a hydrogen or halogen atom or an alkyl, alkylthio, nitro,hydroxyl or cyano radical,R₁₇ represents an alkyl radical or a--CH(R₅)--CO--R₆ residue, R₁₈ represents a pyridyl radical or phenylradical optionally substituted by at least one substituent selected fromamong halogen atoms and alkyl, alkoxy, hydroxyl, carboxyl, and nitroradicals, which comprises reacting a compound of the formula I accordingto claim 1 with a compound of formula ##STR10## in which A is as definedabove for formula II, wherein the reaction is carried out in an inertsolvent, at a temperature of between about 20° C. and the boiling pointof the solvent.
 17. (Tetra-n-Butyl)-ammonium1-(3-aminophenyl)ethanesulphonate (laevorotatory isomer).